Silicone hydrogels are currently widely used materials in ophthalmic lenses. Several brands are available in the commercial market place. While patient comfort has driven the market use of these lenses, the modality for use of these lenses depends on both the physical properties (including oxygen transport and lubricity of the lens) as well as the amount of undesired protein and lipid deposition on the lenses during wear. In a silicone hydrogel contact lens the oxygen transport property which has been correlated to lens comfort can be successfully accessed by using designed silicone and/or perfluorinated compounds while the wettability and or lubricity can be achieved by different methods of surface modification or by incorporation of hydrophilic components in the hydrogel composition. Different technologies exist today to present final silicone hydrogel lenses that have the optical clarity and desired lubricity with controllable modulus and high oxygen transmissibility.
Adsorption of unwanted components from the ocular tear fluid on to the lens material during wear is one of the contributing factors for reduced comfort experienced by patients. In addition, bacterial infections can potentially occur if lens care regimens are not followed for use of the lenses. The extent of undesirable adsorptions will determine the lens care needs for a specific lens and impact on the duration the ophthalmic lens can be present in the eye without causing blurring or discomfort.
Polymerizable antimicrobial silicone hydrogel compounds are of great utility in contact lens formulations to support new generation commercial ophthalmic lenses with reduced lens related infections and that is amenable to extended wear modality. The inherent antimicrobial activity presented by these compounds in an ophthalmic lens should lower the incidence of lens care related ocular infections in patients. Examples ranging from polymerizable quaternium silicone actives to the use of metal salts in lens formulations have been reported in literature, e.g., US 2007/0142583 A1 (Schorzman et al.); US 2008/0182956 A1 (Stanbro et al.); US 2008/0102122 A1 (Mahadevan et al.).
Another important feature that will support extended wear is the incorporation of compounds that show resistance to depositing undesirable proteins and lipids on to the lens. Zwitterionic components such as sulfobetaine and carboxybetaine derivatives have been incorporated in to a polymeric framework to yield coatings that resist protein adsorption with super-low fouling surfaces. See US 2008/011861 A1 (Shaoiyi et al.).
Biomimetic phosphorylcholine (PC) based polymers are known to show much superior anti-fouling properties. Phosphorylcholine based non-silicone hydrogel lenses are commercially available and show minimal protein and lipid spoliation after wear. See WO 92/07885 A1 (Bowers et al.) and Young et al., “Six month clinical evaluation of a biomimetic hydrogel contact lens,” The CLAO Journal, 23(4):226-36 (1997). It has also been reported that silicone intraocular lens (IOL) surface modified by air plasma for binding 2-methacryloxyethyl phosphorylcholine (MPC), in addition to suppressing bacterial adhesion and colonization, improved the hydrophilicity of the IOL. Huang et al., “Surface modification of silicone intraocular lens by 2-methacryloyloxyethyl phosphorylcholine binding to reduce Staphylococcus epidermidis adherence,” Clinical & Experimental Ophthalmology, 35:462-467 (2007). In another study, all four species of human pathogenic microorganisms that are often isolated in association with biomedical device-related infections—that is, Staphylococcus aureus, Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans—were found to have reduced propensity to bind to MPC-coated surfaces than to non-coated surfaces. This was attributed to the effect of “superhydrophilicity” of MPC-coated surfaces. Hirota et al., “Coating of a surface with 2-methacryloyloxyethyl phosphorylcholine (MPC) co-polymer significantly reduces retention of human pathogenic microorganisms,” FEMS Microbiology Letters, 248:37-45 (2005).
The incorporation of phosphorylcholine moiety in to polymerizable silicone compounds combines the beneficial properties of high oxygen permeability of silicones and the lower protein adhesion, hydrophilicity, and antibacterial properties presented by the biostable phosphorylcholine (PC) entity. In addition to reduced protein adsorption, incorporation of PC in polymer systems has also been reported to provide anti-thrombogenic surfaces with reduced platelet adhesion and activations, suitable for use in medical devices. Ishihara et al., “Antithrombogenic polymer alloy composed of 2-methacryloyloxyethyl phosphorylcholine polymer and segmented polyurethane,” Journal of Biomaterials Science: Polymer Edition, 11(11):1183-1195 (2000). Yoneyama et al., “The vascular prosthesis without pseudointima prepared by antithrombogenic phospholipid polymer,” Biomaterials, 23:1455-1459 (2002).
Copolymers of 2-methacryloyl phosphorylcholine (MPC) with n-butylmethacrylate have been reported for use in both in a contact lens body as well as in packaging solutions. The lenses are capable of releasing the hydrophilic polymer from the contact lens for prolonged period of time and have been shown to reduce surface friction. See US 2009/0182067 A1 (Liu). Phosphorylcholine coated silicone hydrogels lenses have been reported to present a very wettable interface indicated by minimal hysterisis between the advancing and receding contact angle. While the uncoated silicone hydrogel show relatively low protein adsorption, the PC coated lenses enhances the effect producing a very low protein-fouling surface. Willis et al., “A novel phosphorylcholine-coated contact lens for extended wear use,” Biomaterials, 22:3261-3272 (2001).
Silicone hydrogels—prepared both by random copolymerization of 2-methacryloyl phosphorylcholine (MPC) with bis(trimethylsiloxy)methylsilylpropyl glycerol methacrylate and as in interpenetrating network (IPN)—were shown to be hydrophilic as well as have protein adsorption resistance which is otherwise prevalent in silicone hydrogels. Super-hydrophilic surfaces were achieved especially in the case of IPN based silicone hydrogels. Shimizu et al., “Super-hydrophilic silicone hydrogels with interpenetrating poly(2-methacryloxyethyl phosphorylcholine) networks,” Biomaterials, 31:3274-3280 (2010).
Almost all the reported chemistries on the use of phosphorylcholine for ophthalmic applications centers on the use of MPC or copolymerization of this monomer with other components. Phase separation of MPC related polymers in a silicone hydrogel framework will need to be overcome to support optically clear ophthalmic lenses with desired functional properties. It is therefore of interest to design silicone monomers and oligomers with in-built phosphorylcholine moieties. The amphiphilic nature of these compounds makes them effective compatibilizers between the silicone and/or fluorinated hydrophobes and the hydrophilic components in a typical lens formulation. The use of such hybrid compounds in Silicone hydrogel formulations enable the formation of contact lenses with higher oxygen transmissibility coupled with superior wettability and reduced lens deposits in comparison to conventional silicone hydrogel lenses.